Sequencing during synthesis (SdS) is an architecture for massively parallel DNA sequencing that has the strong potential of lowering the cost of sequencing enough to allow individuals access to their own genetic heritage as a way of personalizing their medical care. Thus far, however, higher-throughput next-generation sequencing systems are relatively expensive, have relatively long run times and produce relatively short reads, thereby limiting their use for diagnostic applications. This proposal will support the transfer of reagent technology from the Foundation for Applied Molecular Evolution (FfAME) to Intelligent Bio-Systems (IBS), where it will be optimized to yield, at the end of the Phase 2 period, a high-performance prototype instrument that better meets the needs of both the research and healthcare communities. PUBLIC HEALTH RELEVANCE: Sequencing during synthesis (SdS) is an architecture for doing massively parallel DNA sequencing that has the strong potential of lowering the cost of sequencing enough to allow individuals access to their own genetic heritage as a way of personalizing their medical care. Intelligent Bio-Systems (IBS) seeks to become the cost and quality leader in this next generation of DNA sequencing technology. This proposal will support the transfer of reagent technology from the Foundation for Applied Molecular Evolution (FfAME) to IBS, where it will be optimized for the IBS instrument to yield, at the end of the Phase 2 period, a commercial instrument.